Iain Lambert

Research

The overall goal of our research is to investigate mechanisms of chemical toxicity. We are particularly interested in genetic effects. These include examining how chemicals induce mutations, and also determining how different compounds alter gene regulation. Our approaches are primarily molecular, and we apply new technologies to our experimental objectives whenever possible.

Bacterial Nitroreductases

Several nitrosubstituted compounds (NSCs) are potent antimicrobial agents and others are important environmental pollutants. Nitroreductases (NRs) are enzymes that bioactivate NSCs. Our ongoing studies in this area involve cloning and characterizing microbial NRs and examining their mode of regulation. We have shown that NRs may be useful as activating enzymes for Enzyme Prodrug Therapy, a novel cancer chemotherapeutic strategy based on activation of nontoxic prodrugs to cytotoxic products in a tumor-specific manner. MUTAGENESIS AND DNA REPAIR

We have a long-standing interest in determining how compounds that are of considerable human health concern, such as nitroarene, nitroheterocyclic, and aromatic amine compounds, induce mutations. Our approach to this question is primarily molecular biological, and includes the determination of mutational spectra at the DNA sequence level, use of transgenic mouse mutagenesis models, analysis of DNA adducts and metabolites, development of sensitive genotoxicity tests, and the construction of modified DNA substrates that may be used as molecular probes in mutagenesis and DNA repair studies.

Genomics

The success of the genome projects has led to the development of powerful microarray technologies. The application of microarray technology to medicine, drug development, and toxicology will push these disciplines forward at a tremendous pace over the next decade. As part of a group at Health Canada, we are applying microarray technology to the investigation of mechanisms of toxic action, and the development and validation of sensitive biomarkers of exposure. Environmental Microbiology

Persistent chemicals can be biotransformed in soil and aquatic environments by bacteria. This can result in complete or partial degradation of the chemicals (bioremediation), and may diminish the toxicity of complex mixtures in the environment. We are interested in examining the pathways which govern the degradation of nitrosubstituted compounds in the environment, and also in determining the biological activity/toxicity of remediated mixtures.

Mutagenesis and DNA Repair

We have a long-standing interest in determining how compounds that are of considerable human health concern, such as nitroarene, nitroheterocyclic, and aromatic amine compounds, induce mutations. Our approach to this question is primarily molecular biological, and includes the determination of mutational spectra at the DNA sequence level, use of transgenic mouse mutagenesis models, analysis of DNA adducts and metabolites, development of sensitive genotoxicity tests, and the construction of modified DNA substrates that may be used as molecular probes in mutagenesis and DNA repair studies.

Environmental Microbiology

Persistent chemicals can be biotransformed in soil and aquatic environments by bacteria. This can result in complete or partial degradation of the chemicals (bioremediation), and may diminish the toxicity of complex mixtures in the environment. We are interested in examining the pathways which govern the degradation of nitrosubstituted compounds in the environment, and also in determining the biological activity/toxicity of remediated mixtures.